Breast cancer is known as one of the most common cancer in women worldwide. However, it is known that the survival rate of breast cancer patients is higher than those of other cancer patients, when breast cancer is diagnosed early and treated by suitable methods such as surgery. Methods capable of diagnosing breast cancer include X-ray-based mammography, ultrasonic examination, diagnostic imaging techniques such as breast magnetic resonance imaging (MRI), biopsy, and breast self-examination. Mammography has disadvantages in that it is costly and uses radiation. Breast magnetic resonance imaging (MRI) is a safe method that does not use radiation, and is superior to other diagnostic imaging techniques, but incurs high costs that are an obstacle to the popular use of the breast MRI. In addition, biopsy enables accurate cancer diagnosis, but is difficult to use as an early diagnostic method, because it is costly and leaves a scar.
Recent Korean Cancer Statistics indicated that about 32,000 new thyroid cancer patients in the year 2009 occurred and thyroid cancer ranked the first among all types of cancer. Such thyroid cancer patients account for about of new cancer patients in Korea and are expected to further increase in the future. However, thyroid cancer is known to have a very good prognosis, and most thyroid cancers are completely curable, but some thyroid cancers can be very aggressive. Thus, it is important to early diagnose thyroid cancer. Diagnosis starts mainly with clinical and blood test findings and imaging evaluation, and cancer is pathologically diagnosed through fine needle aspiration biopsy or surgery. However, such diagnostic methods are all invasive, costly and not easy to carry out, and a more universal and inexpensive diagnostic method is required. Diagnosis of thyroid cancer using exhaled breath appears to be a non-invasive and inexpensive diagnostic method.
As non-invasive early diagnostic methods for cancer diseases, methods of detecting cancer-specific volatile organic compounds (VOCs) in exhaled breath of cancer patients with lung cancer, breast cancer, head and neck cancer or the like have been actively studied. However, the methods of diagnosing cancer using exhaled breath have not yet been widely used. This is because exhaled breath is mostly composed of nitrogen, oxygen, carbon dioxide and the like, and the concentration of volatile organic compounds (VOCs) in exhaled breath is as very low as nanomolar (10−9 M) or picomolar (10−12 M) concentration, and it is very difficult to find a cancer-specific component in these volatile organic compounds. However, with the recent development of odor sensor technologies such as electronic noses, studies on the possible use of volatile organic compounds (VOCs), contained in human exhaled breath or urine, as indicators of various diseases, particularly cancers, have been conducted.
It is known that substances caused by excessive oxidative stress cause several types of cancer, including breast cancer. Oxidative stress increases the levels of mitochondrial reactive oxygen species (ROSs), and allows these ROSs to be introduced into the cytoplasm to oxidize DNA, protein, etc. Particularly, oxidative stress causes lipid peroxidation of polyunsaturated fatty acids. Substances resulting from this lipid peroxidation are VOCs, including alkane (C4-C20) compounds, methylalkane compounds, etc., and such VOCs are transferred from cellular tissues into the blood circulation system, and some of these VOCs are exhaled as alveolar exhaled breath.
Recent studies reported that breast cancer-specific VOCs detected in exhaled breath include compounds such as alkane (nonane) and methyl alkane (5-methyl tridecane, etc.) (Micheal Phillips, MD, The Breast Journal, 9:184, 2003), as well as 2-propanol,2,3-dyhydro-1-phenyl-4(1H)-quinazolinone, 1-phenyl-ethanone, heptanol, isopropyl myristate, etc. (Micheal Phillips, MD, Breast cancer Research and Treatment, 99:19, 2006). In addition, known carcinogenic compounds, including 3,3-dimethyl pentane, 2-amino-5-isopropyl-8-methyl-1-azulene carbonitrile, 5-(2-methylpropyl) nonane, 2,3,4-trimethyl decane, 6-ethyl-3-octyl ester 2-trifluoro methyl benzoic acid (Hossam Haick, British Journal of Cancer, 103:542, 2010), etc., were detected in breath samples of breast cancer patients, but are difficult to apply to a diagnostic method based on breath detection.
In view of such facts, in Korea, there is an urgent need to develop a method for diagnosing breast cancer, which enables early diagnosis and is inexpensive and non-invasive.
Accordingly, the present inventors have made extensive efforts to develop an inexpensive and non-invasive method for early diagnosing cancer, and as a result, have developed a method of diagnosing cancer by analyzing breast cancer-specific volatile organic compounds (VOCs), which are contained specifically in exhaled breath of cancer patients, by use of an electronic nose based on mass spectrometry, and detecting the presence or absence of the cancer-specific volatile organic compounds in the exhaled breath, thereby completing the present invention.